Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy

Purpose/ObjectivesClinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes.Materials and MethodsPatients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated.ResultsTwenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated.ConclusionsIn our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Characteristics of Particles Emitted from Waste Fires—A Construction Materials Case Study

This study aimed to determine the relative densities of populations of particles emitted in fire experiments of selected materials through direct measurement and parametrization of size distribution as number (NSD), volume (VSD), and mass (MSD). As objects of investigation, four typical materials used in construction and furniture were chosen: pinewood (PINE), laminated particle board (LPB), polyurethane (PUR), and poly(methyl methacrylate) (PMMA). The NSD and VSD were measured using an electric low-pressure impactor, while MSD was measured by weighing filters from the impactor using a microbalance. The parametrization of distributions was made assuming that each distribution can be expressed as the sum of an arbitrary number of log-normal distributions. In all materials, except PINE, the distributions of the particles emitted in fire experiments were the sum of two log-normal distributions; in PINE, the distribution was accounted for by only one log-normal distribution. The parametrization facilitated the determination of volume and mass abundances, and therefore, the relative density. The VSDs of particles generated in PINE, LPB, and PUR fires have similar location parameters, with a median volume diameter of 0.2–0.3 µm, whereas that of particles generated during PMMA burning is 0.7 µm. To validate the presented method, we burned samples made of the four materials in similar proportions and compared the measured VSD with the VSD predicted based on the weighted sum of VSD of raw materials. The measured VSD shifted toward smaller diameters than the predicted ones due to thermal decomposition at higher temperatures.

Preliminary Exploration of Transpedal Lymphangiography With High-Dose Ethiodized Oil Application in the Treatment of Postoperative Chylothorax

Objective: To preliminarily explore the safety and effectiveness of transpedal lymphangiography (TL) with high-dose ethiodized oil application (>20 ml) in the treatment of high-output postoperative chylothorax.Methods: From 1 July 2020 to 1 July 2021, a total of 7 patients with high-flow postoperative chylothorax (> 1,000 ml/d) were retrospectively reviewed in a single center. Clinical data, including surgery types, technical and treatment success of TL, and adverse events of TL, were collected and analyzed.Results: Seven patients (5 cases of non-small cell lung cancer; 2 cases of esophageal carcinoma) with a median age of 62 years (range: 30–70 years) occurred postoperative chylothorax after tumor resection with mediastinal lymphadenectomy. All patients received conservative treatment including total parenteral nutrition and somatostatin administration for a median of 20 days (range: 15–31 days) that failed to cure the chylothorax, so TL was performed as a salvage. Before TL, the median daily chyle output was 1,500 ml/day (range: 1,100–2,000 ml/day). The technical success rate of TL was 100% (7/7), with the median volume of ethiodized oil of 27.6 ml (range: 21.2–30.0 ml) injected in TL. Ruptured thoracic duct was identified in 5 patients (5/7, 71%) in fluoroscopy and chest CT after TL. The treatment success rate of TL was 86% (6/7). In 6 patients, the thoracic drainage was removed after a median of 7 days (range: 4–13 days) from TL performance. No adverse event of TL was reported.Conclusion: Transpedal lymphangiography with high-dose ethiodized oil application (>20 ml) is a feasible, safe, and effective modality for the treatment of high-flow (> 1,000 ml/day) postoperative chylothorax.

Clinical characteristics and outcomes of hyponatraemia associated with oral water intake in adults: a systematic review

IntroductionExcessive water intake is rarely associated with life-threatening hyponatraemia. The aim of this study was to determine the clinical characteristics and outcomes of hyponatraemia associated with excess water intake.MethodsThis review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies (case reports, observational or interventional studies) reporting excess water intake and hyponatraemia in adults (1946–2019) were included.ResultsA total of 2970 articles were identified and 177 were included (88.7% case reports), consisting of 590 patients. The mean age was 46±16 years (95% CI 44 to 48 years), 47% female, 52% had a chronic psychiatric disorder and 31% had no underlying condition. The median volume of water consumed and serum sodium at presentation was 8 L/day (95% CI 8.9 to 12.2 L/day) and 118 mmol/L (95% CI 116 to 118 mmol/L), respectively. The motivator for increased water consumption was psychogenic polydipsia (55%); iatrogenic (13%); exercise (12%); habitual/dipsogenic polydipsia (7%) and other reasons (13%). The clinical features on presentation were severe in 53% (seizures, coma); moderate in 35% (confusion, vomiting, agitation) and mild in 5% (dizziness, lethargy, cognitive deficit) and not reported in 5% of studies. Treatment was supportive in 41% of studies (fluid restriction, treatment of the underlying cause, emergency care), and isotonic and hypertonic saline was used in 18% and 28% of cases, respectively. Treatment-related complications included osmotic demyelination (3%) and rhabdomyolysis (7%), and death occurred in 13% of cases.ConclusionWater intoxication is associated with significant morbidity and mortality and requires daily intake to substantially exceed population-based recommendations. The limitations of this analysis are the low quality and high risk of bias of the included studies.PROSPERO registration numberA pre-existing protocol in the international prospective register of systematic reviews was updated to incorporate any new amendments and reregistered at http://www.crd.york.ac.uk/PROSPERO (registration no. CRD42019129809).

Importance of tranexamic acid in pediatric monosutural craniosynostosis surgery

OBJECTIVE Tranexamic acid (TXA) is an antifibrinolytic drug that has achieved significant reduction in perioperative blood loss and the quantity of blood transfused in many pediatric surgical procedures, without morbidity. Despite the accumulation of evidence regarding its effectiveness in craniosynostosis repair surgery, TXA is not unanimously employed by pediatric neurosurgery teams. The purpose of this study was to evaluate the impact of the routine use of TXA in a homogeneous population of children who underwent open surgery for monosutural craniosynostosis. METHODS The authors retrospectively reviewed 3 cohorts of patients that were subdivided from 2 cohorts surrounding the initiation of TXA (group 1, TXA− [2008–2011] and group 2, TXA+ [2011–2013]) and a third cohort of more recent patients (group 3, TXA+ [2016–2017]). TXA was administered using the same protocol comprising a loading dose of 10 mg/kg over 15 minutes after induction of general anesthesia followed by a 10 mg/kg per hour infusion until skin closure. Patients in all 3 groups underwent similar standardized procedures for scaphocephaly, trigonocephaly, and unicoronal craniosynostosis by the same pediatric neurosurgeon. RESULTS Overall, 102 infants were included in the study: 32 infants in group 1, 36 in group 2, and 34 in group 3. Significant reductions in transfusion of packed erythrocytes (PE) and fresh-frozen plasma (FFP) were observed between the TXA− and TXA+ time periods. The median volume of PE transfusion was reduced by > 50% with the use of TXA (42.8 mL/kg in the TXA− group vs 20.0 in the TXA+ groups, p < 0.0001). Reduction in PE transfusion was 100% postoperatively in the TXA+ groups (20.0 mL/kg in the TXA− group vs 0.0 in the TXA+ groups, p < 0.0001). The median volume of FFP transfusion was reduced by 100% with the use of TXA (12.8 mL/kg in the TXA− group vs 0.0 in the TXA+ groups, p < 0.0001). All children in group 1 received a transfusion, whereas 3 children (8%) and 7 children (20%) in groups 2 and 3, respectively, did not. Significant reductions in postoperative drain output were also noted between the TXA− and TXA+ time periods. The total hospital length of stay was significantly lower in the TXA+ groups (p < 0.0001). CONCLUSIONS Use of TXA reduced blood loss and the need for transfusions but also decreased the hospital length of stay and, thus, minimized overall medical care costs. Intraoperative administration of TXA in craniosynostosis repair surgery should be routinely used in all centers that practice these procedures.

An Evaluation of Total Internal Motions of Locally Advanced Pancreatic Cancer during SABR Using Calypso® Extracranial Tracking, and Its Possible Clinical Impact on Motion Management

(1) Background: the aims of this study were to determine the total extent of pancreatic cancer’s internal motions, using Calypso® extracranial tracking, and to indicate possible clinical advantages of continuous intrafractional fiducial-based tumor motion tracking during SABR. (2) Methods: thirty-four patients were treated with SABR for LAPC using Calypso® for motion management. Planning MSCTs in FB and DBH, and 4D-CTs were performed. Using data from Calypso® and 4D-CTs, the movements of the lesions in the CC, AP and LR directions, as well as the volumes of the 4D-CT-based ITV and the volumes of the Calypso®-based ITV were compared. (3) Results: significantly larger medians of tumor excursions were found with Calypso® than with 4D-CT: CC: 29 mm (p < 0.001); AP: 14 mm (p < 0.001) and LR: 11 mm (p < 0.039). The median volume of the Calypso®-based ITV was significantly larger than that of the 4D-CT based ITV (p < 0.001). (4) Conclusion: beside known respiratory-induced internal motions, pancreatic cancer seems to have significant additional motions which should be considered during respiratory motion management. Only direct and continuous intrafractional fiducial-based motion tracking seems to provide complete coverage of the target lesion with the prescribed isodose, which could allow for safe tumor dose escalation.

Titanium-Enriched Slag Prepared by Atmospheric Hydrochloric Acid Leaching of Mechanically Activated Vanadium Titanomagnetite Concentrates

The titanium-enriched slag was obtained via atmospheric hydrochloric acid leaching of mechanically activated vanadium titanomagnetite concentrates (VTMCs). Under the influence of mechanical activation, specific physicochemical changes were observed via X-ray diffractometry, scanning electron microscopy, and granulometric laser diffraction analysis. Experimental findings revealed that the mechanical activation of VTMCs resulted in a decrease in the median volume particle diameter (d50) and an increase in the specific surface area (SA) with an increased milling time. The results of the leaching experiment revealed that the mechanical activation treatment favors the extraction of iron (Fe) and titanium dioxide (TiO2) from the VTMCs. The Fe and TiO2 extractions from the mechanically activated sample after 10 h compared with the unactivated sample were increased by 12.82% and 4.73%, respectively. The presence of the ilmenite phase in the titanium-enriched slag was confirmed by X-ray diffractometry and EDS patterns, and the content of the TiO2 in the enriched slag can get as high as 43.75%.

Abstract 1122‐000128: Imaging Follow‐Up in Carotid Webs: Is There Vascular Remodeling?

Introduction : Carotid web (CaW) is a shelf‐like fibrotic projection at the carotid bulb and constitutes an underrecognized cause of ischemic stroke. Atherosclerotic lesions are known to have dynamic remodeling with time however, little is known regarding the evolution of CaW over time. We aimed to better understand if CaW is a static or dynamic entity on delayed vascular imaging. Methods : This was a retrospective analysis of the CaW database at our comprehensive stroke center, including patients diagnosed with CaW between September 2014 through June 2021. Patients who had at least two good quality CT angiograms (CTAs) that were at least 6 months apart were included (CTAs with CaW and superimposed thrombus were excluded). CaW were quantified with 3‐D measurements using Horos software. This was done via volumetric analysis of free‐hand delineated CaW borders on thin cuts of axial CTA (Figure 1 Panel A). NASCET criteria was used to evaluate the degree of stenosis. Results : Sixteen CaW in 13 patients were identified and included. The median imaging follow‐up window was 16 months (IQR 12–22, range 6–29). Median patient age was 45.5 years‐old, 69% were women, 25% had hypertension, 38% hyperlipidemia, 25% diabetes mellitus, 0% atrial fibrillation, and 13% active smokers. 75% of the included CaW were symptomatic while 25% were asymptomatic. Median volume of CaW on initial CTA (8.52 mm3 [IQR 3.7‐13], range 2.2‐30.4) was comparable to median volume of CaW on most recent CTA (8.47 mm3 [IQR 4.0‐12.8], range 2.3‐29.4; p = <0.001 (Figure 1 Panel B). The CaW volumetric measurement correlation between the initial and most recent CTA was near perfect (rs = ‐0.99, p = <0.001). The median change in measured volume of CaW between first and last CTA was ‐0.19 mm3 [IQR ‐0.6‐0.4], range ‐1‐0.8. Median degree of stenosis was 8.1% [IQR 4.5‐17.1], range 0.4‐31.2. The duration of follow‐up imaging was not correlated with the change in CaW volume (Kendall tau‐b[τb] = ‐0.17, p = 0.93). The initial CaW volume was not found to be correlated to the degree of stenosis (τb = ‐0.08, p = 0.65). Conclusions : The volume of the CaW was not found to change over time, reinforcing the idea that this is a relatively static lesion. The CaW volume was not found to correlate with the degree of stenosis caused by it. Further longitudinal studies with longer follow‐up intervals are warranted.

Quantification of Fluid Volume and Distribution in the Paediatric Colon via Magnetic Resonance Imaging

Previous studies have used magnetic resonance imaging (MRI) to quantify the fluid in the stomach and small intestine of children, and the stomach, small intestine and colon of adults. This is the first study to quantify fluid volumes and distribution using MRI in the paediatric colon. MRI datasets from 28 fasted (aged 0–15 years) and 18 fluid-fed (aged 10–16 years) paediatric participants were acquired during routine clinical care. A series of 2D- and 3D-based software protocols were used to measure colonic fluid volume and localisation. The paediatric colon contained a mean volume of 22.5 mL ± 41.3 mL fluid, (range 0–167.5 mL, median volume 0.80 mL) in 15.5 ± 17.5 discreet fluid pockets (median 12). The proportion of the fluid pockets larger than 1 mL was 9.6%, which contributed to 94.5% of the total fluid volume observed. No correlation was detected between all-ages and colonic fluid volume, nor was a difference in colonic fluid volumes observed based on sex, fed state or age group based on ICH-classifications. This study quantified fluid volumes within the paediatric colon, and these data will aid and accelerate the development of biorelevant tools to progress paediatric drug development for colon-targeting formulations.

Changes in the Intra-Amniotic Pressure following Transabdominal Amnioinfusion during Pregnancy

<b><i>Objective:</i></b> The aim of the article was to investigate the changes in intra-amniotic pressure following transabdominal amnioinfusion during pregnancy. <b><i>Design:</i></b> This retrospective study included 19 pregnant women who underwent transabdominal amnioinfusion during pregnancy to relieve umbilical cord compression and improve the intrauterine environment or to increase the accuracy of ultrasonography. <b><i>Materials and Methods:</i></b> We measured and analyzed the changes in intra-amniotic pressure, single deepest pocket, and the amniotic fluid index before and after amnioinfusion. We also determined the incidence of maternal or fetal adverse events, such as preterm premature rupture of membranes, preterm delivery, fetal death within 48 h, placental abruption, infection, hemorrhage, and peripheral organ injury. <b><i>Results:</i></b> A total of 41 amnioinfusion procedures were performed for 19 patients. The median gestational age during the procedure was 24.3 weeks. The median volume of the injected amniotic fluid was 250 mL. The median single deepest pocket and amniotic fluid index after amnioinfusion were significantly higher than those before amnioinfusion (4.0 cm vs. 2.65 cm; <i>p</i> &#x3c; 0.001 and 13.4 cm vs. 6.0 cm; <i>p</i> &#x3c; 0.001). However, the median (range) intra-amniotic pressure after amnioinfusion was not significantly different compared to that before amnioinfusion (11 mm Hg vs. 11 mm Hg; <i>p</i> = 0.134). Maternal or fetal adverse events were not observed following amnioinfusion. <b><i>Conclusion:</i></b> Intra-amniotic pressure remained unchanged following amnioinfusion. The complications associated with increased intra-amniotic pressure are not likely to develop if the amniotic fluid index and/or single deepest pocket remains within the normal range after amnioinfusion. Studies of groups with and without complications are warranted to clarify the relationship between the intra-amniotic pressure and incidence of complications.